EUFOREA/EPOS2020 statement on the clinical considerations for chronic rhinosinusitis with nasal polyps care.

Following the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) treatment algorithm for chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), patients suffering from severe uncontrolled CRSwNP are recommended to receive oral corticosteroids, (revision) sinus surgery, systemic biologicals and/or aspirin treatment after desensitization (ATAD). Given the major differences in indications, outcomes, practical considerations, risks and costs of these key pillars of treatment, there is a growing need to define criteria for each treatment option and list the clinically relevant and major considerations for them. This EUFOREA document therefore provides an expert panel overview of the expected outcomes, specific considerations and (contra)indications of the five major treatment arms of severe uncontrolled CRSwNP: oral corticosteroids, primary and revision sinus surgery, biological treatment and ATAD. This overview of treatment considerations is needed to allow physicians and patients to consider the different options in the context of providing optimal and personalized care for severe uncontrolled CRSwNP. In conclusion, the five major treatment options for severe uncontrolled CRSwNP have intrinsic advantages, specific indications and considerations that are of importance to the patient, the physician and the society. This EUFOREA statement supports the unmet need to define criteria for the indication of every treatment pillar of CRSwNP.

The Unified Airway Hypothesis: Evidence From Specific Intervention With Anti-IL-5 Biologic Therapy.

The unified airway hypothesis proposes that upper and lower airway diseases reflect a single pathological process manifesting in different locations within the airway. Functional, epidemiological, and pathological evidence has supported this well-established hypothesis for some time. However, literature on the pathobiologic roles/therapeutic targeting of eosinophils and IL-5 in upper and lower airway diseases (including asthma, chronic rhinosinusitis with nasal polyps [CRSwNP], and nonsteroidal anti-inflammatory drug-exacerbated respiratory disease) has recently emerged. This narrative review revisits the unified airway hypothesis by searching the scientific literature for recent learnings and clinical trial/real-world data that provide a novel perspective on its relevance for clinicians. According to the available literature, eosinophils and IL-5 have important pathophysiological roles in both the upper and lower airways, although the impact of eosinophils and IL-5 may vary in asthma and CRSwNP. Some differential effects of anti-IL-5 and anti-IL-5-receptor therapies in CRSwNP have been observed, requiring further investigation. However, pharmaceutical targeting of eosinophils and IL-5 in patients with upper, lower, and comorbid upper and lower airway inflammation has led to clinical benefit, supporting the hypothesis that these are linked conditions manifesting in different locations. Consideration of this approach may improve patient care and aid clinical decision making.

New Developments in Allergic Fungal Rhinosinusitis Pathophysiology and Treatment.

BACKGROUND: Allergic fungal rhinosinusitis (AFRS) is an endotype of chronic rhinosinusitis (CRS) with nasal polyps characterized by eosinophilic mucin laden with fungal hyphae entrapped in expanded sinus cavities with an exaggerated hypersensitivity to fungal elements. The last decade has elucidated fungi-driven inflammatory pathways contributing to the pathophysiology of chronic inflammatory respiratory diseases. In addition, novel therapeutic biologic options have become available for CRS over the last several years. OBJECTIVE: To review the current literature examining AFRS, focusing on recent developments in our understanding of its pathophysiology and implications for treatment options. METHODS: Review article. RESULTS: Fungi-driven respiratory inflammation has been linked to fungal proteinases and toxin activity. In addition, AFRS patients demonstrate a local sinonasal immunodeficiency in antimicrobial peptides and hence limited antifungal activity, along with an exaggerated type 2 inflammatory response, highlighting a possible imbalanced type 1, type 2, and type 3 profile. The elucidation of these dysregulated molecular pathways has highlighted novel potential therapeutic targets. As such, the clinical management of AFRS, which once included surgery and extended courses of oral corticosteroids, is transitioning away from long courses of oral corticosteroids to incorporate novel delivery mechanisms of topical therapeutic targets and biologics for recalcitrant disease. CONCLUSION: AFRS is an endotype of CRS with nasal polyps (CRSwNP) for which the molecular pathways leading to its inflammatory dysfunction are beginning to be illuminated. In addition to affecting treatment options, these understandings may shape necessary changes to diagnostic criteria and the extrapolated effects of environmental changes on AFRS. More critically, a better appreciation of fungi-driven inflammatory pathways may have implications for the understanding of broader CRS inflammation.

Update on allergic fungal rhinosinusitis.

Allergic fungal rhinosinusitis (AFRS) is a unique clinical entity that falls under the broader umbrella of chronic rhinosinusitis with nasal polyps with type 2 inflammation. It is characterized by nasal polyposis, production of characteristic thick eosinophilic mucin, and expansile change of involved sinus cavities. The diagnosis is classically made using the Bent and Kuhn criteria. However, recent studies have indicated the lack of specificity of some major criteria. The need to fulfill all 5 criteria before diagnosing AFRS partially mitigates this but renders the criteria cumbersome to use, and highlights the need to develop more specific criteria. Our understanding of AFRS pathophysiology has advanced significantly and has helped elucidate the lack of histatins contributing to the inability to clear fungal spores, consequently leading to fungi-induced disruption of the epithelial barrier and stimulation of sinonasal epithelial cells. These trigger a cascade of type 2 inflammatory cytokines driven by both the adaptive and innate immune system. Although more research is needed, these findings could hypothetically point to a limited type 3 immune response at the sinus mucosa, resulting in a compensatory overstimulation of type 2 inflammatory processes. Treatment for AFRS remains centered on surgery and topical corticosteroids. Short courses of systemic corticosteroids may be used with caution, and fungal-specific immunotherapy and systemic antifungals are options in recalcitrant disease. Biologics show early promise, as we await data from randomized controlled trials under way. Finally, new insights into AFRS pathology provide opportunities for novel therapeutic strategies.

The Joint Task Force on Practice Parameters GRADE guidelines for the medical management of chronic rhinosinusitis with nasal polyposis.

These evidence-based guidelines support patients, clinicians, and other stakeholders in decisions about the use of intranasal corticosteroids (INCS), biologics, and aspirin therapy after desensitization (ATAD) for the management of chronic rhinosinusitis with nasal polyposis (CRSwNP). It is important to note that the current evidence on surgery for CRSwNP was not assessed for this guideline nor were management options other than INCS, biologics, and ATAD. The Allergy-Immunology Joint Task Force on Practice Parameters formed a multidisciplinary guideline panel balanced to include the views of multiple stakeholders and to minimize potential biases. Systematic reviews for each management option informed the guideline. The guideline panel used the Grading of Recommendations Assessment, Development and Evaluation approach to inform and develop recommendations. The guideline panel reached consensus on the following statements: (1) In people with CRSwNP, the guideline panel suggests INCS rather than no INCS (conditional recommendation, low certainty of evidence). (2) In people with CRSwNP, the guideline panel suggests biologics rather than no biologics (conditional recommendation, moderate certainty of evidence). (3) In people with aspirin (nonsteroidal anti-inflammatory drug)-exacerbated respiratory disease, the guideline panel suggests ATAD rather than no ATAD (conditional recommendation, moderate certainty of evidence). The conditions for each recommendation are discussed in the guideline.

Three-Dimensional Printed Models to Accelerate Resident Surgical Learning Curve for Standard Endoscopic Sinus Surgery Techniques.

Background: Endoscopic sinus surgery presents significant visuospatial challenges to surgical trainees. We tested the utility of novel 3D printed models to simulate sinus surgery tasks to improve endoscopic skillsets in resident trainees. Methods: This was a prospective quality improvement study of 10 ENT residents (PGY1-5). Participants rotated through 4 stations with different 3D simulation training modules designed to enhance endoscopic skillsets in the axial, sagittal and coronal planes (e.g., straight forceps to grasp a bead from a ledge, angled instruments to cannulate openings). Participants completed a self-assessment survey on the subjective sinus surgical skills using a visual analog scale before and after tasks. Two- tailed paired T-tests were used to analyze the data. Results: All residents rated their post-intervention "overall sinus surgery skills" higher than pre-intervention. They rated simulations to provide more significant utility as an adjunct to surgical education after the intervention. All but one participant reported improved spatial awareness working with the endoscopes and surgical instruments. There was subjectively improved proficiency in using 0-degree and angled endoscopes as well as cutting, grasping, and curved instruments after the intervention. The simulations led to subjective improvements in spatial awareness, bimanual dexterity, and increased confidence in selecting correct surgical instruments. Conclusion: Our set of novel 3D printed models to improve sinus surgery skillset was well accepted by the resident cohort. The 3D models can serve as an adjunct tool to traditional residency education.

Allergic Fungal Rhinosinusitis: The Role and Expectations of Biologics.

Allergic fungal rhinosinusitis (AFRS) is a noninvasive subtype of chronic rhinosinusitis with nasal polyps (CRSwNP) that usually develops in immunocompetent atopic individuals and is more common in geographic regions characterized by warm temperatures and high humidity, conducive to higher environmental fungal presence. Allergic fungal rhinosinusitis usually presents with unique computed tomography findings and significant polyp burden, yet patients often report minimal sinus symptoms. Patients with AFRS often have extremely elevated serum total and fungal-specific IgE levels. Treatment almost always requires surgery, in which adjuvant medical therapy is critical to success. However, until recently the choice of adjuvant therapy has consisted primarily of either oral and/or topical steroids. Although oral corticosteroids decrease recurrence after surgery, data for the effectiveness of other adjunctive pharmacologic agents, including topical and oral antifungal agents and immunotherapy, have remained unclear and hence are not recommended in recent guidelines including the International Consensus of Allergy and Rhinology. Three biologics, omalizumab, dupilumab, and mepolizumab, have recently been approved for treating CRSwNP in general, but clinical trials to date with these biologics did not involve AFRS patients. Recently published case reports and smaller prospective studies have shown good efficacy of these biologics on the AFRS subgroup of patients. This article provides an overview of the understanding of the pathophysiology of AFRS, implications of this understanding on the possible role of biologics, and clinical reports on the use of biologics in treating AFRS. Because biologics are indicated for treating CRSwNP, follow up real-world evidence studies are needed for AFRS.

Topical corticosteroids for chronic rhinosinusitis with nasal polyposis: GRADE systematic review and network meta-analysis.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is associated with a significant disease burden. The optimal use of and administration route for intranasal corticosteroids (INCS) when managing CRSwNP are unclear. OBJECTIVE: We systematically synthesized the evidence addressing INCS for CRSwNP. METHODS: We searched studies archived in Medline, Embase, and Central from database inception until September 1, 2021, for randomized controlled trials comparing INCS using any delivery method to placebo or other INCS administration types. Paired reviewers screened records, abstracted data, and rated risk of bias (CLARITY revision of Cochrane Risk of Bias version 1 tool) independently and in duplicate. We synthesized the evidence for each outcome using random effects network meta-analyses. We critically appraised the evidence following the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) approach. RESULTS: We analyzed 61 randomized controlled trials (7176 participants, 8 interventions). Sinusitis-related quality of life might improve with INCS rinse (mean difference [MD] -6.83, 95% confidence interval [CI] -11.94 to -1.71) and exhalation delivery system (EDS) (MD -7.86, 95% CI -14.64 to -1.08) compared to placebo (both low certainty evidence). Nasal obstruction symptoms are likely improved when receiving INCS via stent/dressing (MD -0.31, 95% CI -0.54 to -0.08), spray (MD -0.51, 95% CI -0.61 to -0.41), and EDS (MD -0.35, 95% CI -0.51 to -0.18) (all moderate to high certainty) compared to placebo. We found no important differences in adverse effects among interventions (moderate certainty for INCS spray, very low to low certainty for others). CONCLUSIONS: Multiple delivery forms of INCS are viable therapeutic options for CRSwNP, resulting in improvement of patient-important outcomes. INCS via stent, spray, and EDS appear to be beneficial across the widest range of considered outcomes.

Indications for absorbable steroid-eluting sinus implants: Viewpoint via the Delphi method.

Absorbable steroid-eluting sinus implants provide targeted corticosteroid release over a sustained period and are designed to prevent both undesirable adhesion formation and sinus ostia restenosis. Here, we highlight the key evidence of these implants to date and query a group of experts via a Delphi process on the indications and optimal timing for intraoperative or in-office placement of these implants. Six of a total of 12 statements reached consensus and were accepted. Overall, experts largely agree that intraoperative or in-office use of steroid-eluting stents could be considered for patients: (1) who are diabetic or intolerant of oral steroids, (2) undergoing extended frontal sinus surgery, and (3) with recurrent stenosis. Given the lack of expert consensus on other key statements, clinicians should carefully consider these treatment options on a case-by-case basis after shared decision-making.

A Comparison of International Guidelines for Rhinosinusitis.

The European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS), latest version EPOS2020, and the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR-RS), latest version ICAR-RS-2021, assimilate thousands of articles on the topic of rhinosinusitis. Encompassing scores of subtopics and relying on the perspectives of many international experts, EPOS2020 and ICAR-RS-2021 reduce the existing data into consumable formats and create evidence-based recommendations. The approaches and findings are similar in many respects but have significant differences. This clinical commentary, authored by some of the principal authors of these documents, compares and contrasts EPOS2020 and ICAR-RS-2021, examining methodology, diagnostic and treatment recommendations, and each document's emphases. This commentary demonstrates that, through somewhat differing methodologies, the 2 documents arrive at largely similar conclusions. Those who care for patients suffering from rhinosinusitis will find the documents complementary and valuable in their differences as much as in their similarities.

Aerosol Production with Surgical Instrumentation: Implications for Head and Neck Surgery in the COVID-19 Era.

Evaluating the aerosolization of droplets from surgical instruments to assess the implications of surgery in SARS-CoV-2 transmission for both patients and providers. Cadaver study. Outpatient surgery center. Aerosolized particles between 0.3 and 25 microns were measured. Instruments tested included monopolar cautery with and without suction, bipolar cautery, a bipolar vessel sealing device, and tissue scissors. Each trial was compared to a background reading. Monopolar cautery without suction, Ligasure used continuously and Bipolar cautery produced the most aerosols. Monopolar cautery with simultaneous suction produced no detectable aerosols. Ligasure used for a single cycle produced notably fewer aerosols than during continuous use. Most aerosols produced were < 5 microns. These data support n95 use during surgical management of the upper aerodigestive tract, as well as the use of suction in the surgical field.

Contour Map Point Distribution and Surgeon Experience Level Affect Accuracy of Surgical Navigation in a Pilot Study.

BACKGROUND: Reliable use of surgical navigation depends upon the registration process. The gold standard is paired-point registration with bone-anchored fiducials, but contour-map registration is more practical. Surgeons may employ variable contour maps and less experienced team members often perform this critical step. The impact of these practices on target registration error (TRE) is not well-studied. METHODS: A dry lab set-up consisting of a navigation system (Fusion ENT, Medtronic, Jacksonville, FL) and a sinus phantom with 2 mm radiopaque spheres in the sphenoid and ethmoid regions was developed. A CT (0.625 mm slice thickness) was obtained. Registration was performed with a contour-based protocol. Accuracy was determined using the software's distance measurement tool. Registration was performed with narrow-field (NF; forehead points medial to the mid-pupillary line) and wide field (WF; entire forehead) contour maps. An experienced rhinologist and a resident surgeon performed each registration in triplicate and TRE at the sphenoid and ethmoid markers was measured in triplicate. RESULTS: WF mapping had a lower TRE than NF (1.09 mm [95% Confidence Interval (CI) 0.96-1.22] vs 1.68 mm [95% CI 1.50-1.86]). The experienced surgeon had a lower TRE compared to the resident (1.21 mm [95% CI 1.08-1.34] vs 1.54 mm [95% CI 1.35-1.74]). CONCLUSIONS: In this navigation model, wide field mapping offers better accuracy than narrow-field mapping, and an experienced surgeon seemed to achieve better accuracy than a resident surgeon. These observations have potential implications for the use of this technology in the operating room.

Are nonsteroidal anti-inflammatory drugs effective enough for postoperative pain control after functional endoscopic sinus surgery and septoplasty? A randomized, controlled study.

BACKGROUND: Endoscopic sinus surgery (ESS) and septoplasty are commonly performed procedures without standardized postoperative pain regimens. There is reluctance to prescribe opioids for postoperative pain given their potential for abuse. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been demonstrated to reduce or even obviate the need for opioid pain medications after otolaryngologic surgeries, but prospective validation is lacking. METHODS: A randomized, controlled study comparing the efficacy of diclofenac sodium to hydrocodone/acetaminophen (APAP) after ESS with or without septoplasty was performed. Participants were given a 100-mm visual analog pain scale (VAS) at postoperative days (PODs) 1, 2, 3, and 5 after ESS. Two-sample t tests were used to compare pain scores between groups. RESULTS: One hundred patients enrolled, and 74 patients provided pain scores to the survey. Pain was greatest for both groups on POD 1. Treatment with diclofenac sodium vs hydrocodone/APAP did not statistically impact pain scores at PODs 1, 2, 3, or 5. No cases of epistaxis requiring an emergency room visit or return to the operating room were noted during the study period. CONCLUSION: Diclofenac sodium may be non-inferior to hydrocodone/APAP in treating pain after ESS with or without septoplasty in opioid naive patients without pre-existing pain conditions. Further studies with larger samples are warranted to investigate the potential superiority of diclofenac to hydrocodone/APAP in certain patients after ESS and septoplasty.

The role of fungus in the pathogenesis of chronic rhinosinusitis.

PURPOSE OF REVIEW: The etiologic role of fungi in chronic rhinosinusitis remains controversial. The purpose of this review is to further our understanding of molecular immunologic pathways activated by fungi and clinical trials of antifungals in severe subtypes of asthma and allergic fungal rhinosinusitis. RECENT FINDINGS: Various fungal components such as protease and chitin are capable of eliciting a type 2 innate and adaptive immune response. However, definitive studies on the etiologic role of fungi in chronic rhinosinusitis (CRS) is dependent on the development of a fungi-induced murine model of CRS. Short of this model, extrapolations of observations and results from clinical trials in fungi-induced asthma subtypes support a key role of fungi in the pathophysiology of allergic fungal rhinosinusitis and possibly other CRS endotypes. SUMMARY: Fungi plays a key role in the pathophysiology of several subtypes of chronic inflammatory respiratory diseases. However, a fungi-induced murine model of CRS is needed to explicitly investigate the molecular pathways and potential therapeutic targets.

Biologics for chronic rhinosinusitis with nasal polyps: Economics and ethics.

Biologics have recently been approved for use in chronic rhinosinusitis with nasal polyps patients. While effective in controlling disease on subjective and objective short-term outcome measures, limited data suggest that biologics have the potential to be used long term. The current wholesale acquisition costs for biologics are quite high. Widespread, prolonged use of these medications may create a large burden to our healthcare system. Cost-effectiveness analyses, particularly for specific patient cohorts, are needed to determine appropriate use of these medications. The ethics of patient preference of various treatment options, counseling regarding side effect profiles, and healthcare economics also need to be addressed.

Revisiting the controversy: The role of fungi in chronic rhinosinusitis.

In the last two decades, the development of culture-independent genomic techniques has facilitated an increased appreciation of the microbiota-immunity interactions and their role in a multitude of chronic inflammatory diseases such as chronic rhinosinusitis (CRS), asthma, inflammatory bowel disease and dermatitis. While the pathologic role of bacteria in chronic inflammatory diseases is generally accepted, the understanding of the role of fungi remains controversial. Chronic rhinosinusitis, specifically the phenotype linked to nasal polyps, represents a spectrum of chronic inflammatory diseases typically characterized by a type 2 immune response. Studies on the microbiota within sinus cavities from healthy and diseased patients have focused on the bacterial community, mainly highlighting the loss of diversity associated with sinus inflammation. Within the various CRS with nasal polyps (CRSwNP) phenotypes, allergic fungal rhinosinusitis presents an opportunity to investigate the role of fungi in chronic type 2 immune responses as well as the antifungal immune pathways designed to prevent invasive fungal diseases. In this review, we examine the spectrum of fungi-associated sinus diseases highlighting the interaction between fungal species and host immune status on disease presentation. With a focus on fungi and type 2 immune response, we highlight the current knowledge and its limitations of the sinus mycobiota along with cellular interactions and activated molecular pathways linked to fungi.

The immune response to airway mycosis.

The allergic airway diseases chronic rhinosinusitis (CRS), allergic fungal rhinosinusitis (AFRS), asthma, allergic bronchopulmonary mycosis/aspergillosis (ABPM/A), and cystic fibrosis (CF) share a common immunological signature marked by TH2 and TH17 cell predominant immune responses, the production of IgE antibody, and a typical inflammatory cell infiltrate that includes eosinophils and other innate immune effector cells. Severe forms of these disorders have long been recognized as being related to hypersensitivity reactions to environmental fungi. Increasingly however,environmental fungi are assuming a more primary role in the etiology of these disorders, with airway mycosis, a type of non-invasive airway fungal infection, recognized as an essential driving factor in at least severe subsets of allergic airway diseases. In this review, we consider recent progress made in understanding the immune mechanisms that drive airway mycosis-related diseases, improvements in immune-based diagnostic strategies, and therapeutic approaches that target key immune pathways.

N95 respirator reuse, decontamination methods, and microbial burden: A randomized controlled trial.

PURPOSE: To evaluate the effectiveness and ease of N95 respirator decontamination methods in a clinic setting and to identify the extent of microbial colonization on respirators associated with reuse. METHODS: In a prospective fashion, N95 respirators (n = 15) were randomized to a decontamination process (time, dry heat, or ultraviolet C light [UVC]) in outpatient clinics. Each respirator was re-used up to 5 separate clinic sessions. Swabs on each respirator for SARS-CoV-2, bacteria, and fungi were obtained before clinic, after clinic and post-treatment. Mask integrity was checked after each treatment (n = 68). Statistical analyses were performed to determine factors for positive samples. RESULTS: All three decontamination processes reduced bacteria counts similarly. On multivariate mixed model analysis, there were an additional 8.1 colonies of bacteria (95% CI 5.7 to 10.5; p < 0.01) on the inside compared to the outside surface of the respirators. Treatment resulted in a decrease of bacterial load by 8.6 colonies (95% CI -11.6 to -5.5; p < 0.01). Although no decontamination treatment affected the respirator filtration efficiency, heat treatments were associated with the breakdown of thermoplastic elastomer straps. Contamination with fungal and SARS-CoV-2 viral particles were minimal to non-existent. CONCLUSIONS: Time, heat and UVC all reduced bacterial load on reused N95 respirators. Fungal contamination was minimal. Heat could permanently damage some elastic straps making the respirators nonfunctional. Given its effectiveness against microbes, lack of damage to re-treated respirators and logistical ease, UVC represents an optimal decontamination method for individual N95 respirators when reuse is necessary.

Gender and authorship trends in rhinology, allergy, and skull-base literature from 2008 to 2018.

BACKGROUND: A recent analysis suggested potential narrowing of the gender gap in research productivity in the field of rhinology. This analysis did not, however, provide insight into how the genders are represented in the rhinologic literature. This study aimed to evaluate 11 years of literature to evaluate for gender differences in authorship position, collaborations, category and content of research, citations, and funding to gain perspective on how gender and authorship has changed over time. METHODS: Authorship data for all articles on rhinologic subject matter published between January 1, 2008 and December 31, 2018 in four otolaryngology journals was collected. The gender of authors was determined by protocol. Category and content of research and funding status/source were additionally obtained. RESULTS: Data were collected from 2666 articles. Gender of 14,510 authors was determined. Female authors accounted for 23% of the overall authors and male authors accounted for 77%. Female first authorship increased significantly over time, but there was no change in female senior authorship. The percentage of female authors steadily increased over time, whereas male authorship decreased slightly. Mixed gender teams were shown to be increasing in frequency. Women published more than expected in basic science and allergy and less than expected in skull base. On funded studies, women were significantly underrepresented as senior authors. CONCLUSION: This study represents the first assessment of gender differences in the rhinology literature. Areas where female representation can improve include senior authorship, increased involvement in skull base publications, and increased funding.